Helix-forming peptides

Fig. 8. De novo designed a-hehcal proteins. Dimers of the amphiphilic helix-forming peptide a B, GELEELLKKLKELLKG (see Table 1), in which the nature of the linker connecting the individual heflces plays a critical role in the stmcture of the final protein, (a) Using a Pro residue as the linker, ie, a B-Pro-a B, three molecules aggregated to form a trimeric coded-cod. (b) Using Pro-Arg-Arg as the linker, ie, a B-Pro-Aig-Arg-a, resulted in the...

Selected entries from Methods in Enzymology [vol, page(s)] Electron paramagnetic resonance [effect on line width, 246, 596-598 motional narrowing spin label spectra, 246, 595-598 slow motion spin label spectra, 246, 598-601] helix-forming peptides, 246, 602-605 proteins, 246, 595 Stokes-Einstein relationship, 246, 594-595 temperature dependence, 246, 602, 604. 

Kojima S, Kuriki Y, Yazaki K, Miuia K-I. Stabilization of the fibrous structure of an a-helix-forming peptide by sequence reveral. Biochem Biophys Res Commun 2005 331 577-582. 

In our laboratory we have been studying the physical characteristics of helix-forming peptides. In 1989 it was found that alanine-based peptides form helices in aqueous solution.This is a key discovery because these peptides can now be used as simple model systems for understanding protein folding, structure, and dynamics. It is generally believed that... 

Spin label EPR may also be used to map geometry in helical peptides. When helix-forming peptides were first discovered, it was assumed that... 

One recent example is a HF EPR study of nitroxide side-chain dynamics in a helix-forming peptide which was labeled with MTSSL." The experimental spectra recorded at 140 GHz from 277 to 306 K were found to be amenable to... 

The effect of C ,C -disubstituted amino acids (aaAAs) on peptide secondary structure has been studied in recent years.2a d While longer side-chain C ,C -di-n-alkyl amino acids promote extended peptide conformation,23 alicyclic aaAAs, in which the Ca carbon forms a cyclic bridge with itself, such a 1-aminocyclopentane-l-carboxylic acid (Ac5c) and 1-aminocyclohexane-l-carboxylic acid (Ac6c), have helix-forming characteristics similar to those of 1 -aminoisobutyric acid (Aib).2ax... 

Fig. 2.12 The j8-peptide 3,4-helical structure. (A) Stereo-view along the helix axis of the left-handed 3,4-helix formed by, 8 -peptide 66 in solution as determined by NMR in CD3OH (adapted from [103, 154]). Side-chains have been omitted for clarity. (B) Top view.

Fig. 2.23 Model of the 2g-helix formed by all-w/i///ce-jff -peptide 109 generated with ideal torsion angle values =-135°, =58°,...

WiTTUNG P., Nielsen P. E., Buchardt O., Egholm M., Norden B. DNA-like double helix formed by peptide nucleic acid. Nature 1994, 368 561-563. 

Bierzynski, Kim PS, Baldwin RL (1982) A salt bridge stabilizes the helix formed by isolated C-peptide of RNase A. Proc Natl Acad Sci USA 79 2470-2474. 

Further evidence for these a-helix ROA band assignments in the extended amide III region comes from the ROA spectrum of poly-L-alanine dissolved in a mixture of chloroform (70%) and dichloracetic acid (30%), known to promote a-helix formation (Fasman, 1987), which shows strong positive ROA bands at 1305 and 1341 cm-1 (unpublished results), and of the cv-helix forming alanine-rich peptide AK21 (sequence Ac-AAKAAAAKAAAAKAAAAKAGY-NHg) in aqueous solution which shows strong positive ROA bands at 1309 and 1344 cm-1 (Blanch et al., 2000). 

If this hypothesis is true, one could expect the solvent-accessible surface area (ASA) of the polypeptide backbone in the PPII conformation to be correlated with measured PPII helix-forming propensities. In order to test this, Monte Carlo computer simulations of short peptides Ac-Ala-Xaa-Ala-NMe (Xaa = Ala, Asn, Gin, Gly, lie, Leu, Met, Pro, Ser, Thr, and Val) were run. These particular residues were examined because their... 

PPII helix-forming propensities have been measured by Kelly et al. (2001) and A. L. Rucker, M. N. Campbell, and T. P. Creamer (unpublished results). In the simulations the peptide backbone was constrained to be in the PPII conformation, defined as (0,VO = ( — 75 25°, +145 25°), using constraint potentials described previously (Yun and Hermans, 1991 Creamer and Rose, 1994). The AMBER/ OPLS potential (Jorgensen and Tirado-Rives, 1988 Jorgensen and Severance, 1990) was employed at a temperature of 298° K, with solvent treated as a dielectric continuum of s = 78. After an initial equilibration period of 1 x 104 cycles, simulations were run for 2 x 106 cycles. Each cycle consisted of a number of attempted rotations about dihedrals equal to the total number of rotatable bonds in the peptide. Conformations were saved for analysis every 100 cycles. Solvent-accessible surface areas were calculated using the method of Richmond (1984) and a probe of 1.40 A radius. 

The sum of the estimated average solvent-accessible surface areas, (ASA), for the peptide units (—CO—NH—) on either side of residue Xaa, plus the Ca of Xaa, in each peptide simulated are given in Table II. Also shown are the estimated PPII helix-forming propensities for each residue measured by Kelly et al. (2001) and A. L. Rucker, M. N. Campbell, and... 

Estimated PPII Helix-Forming Propensities and Average Sum of Backbone ASAs from Monte Carlo Computer Simulations of Peptides Ac-Ala-Xaa-Ala-NMe Restricted to the PPII Conformation11... 

Other than an effect on backbone solvation, side chains could potentially modulate PPII helix-forming propensities in a number of ways. These include contributions due to side chain conformational entropy and, as discussed previously, side chain-to-backbone hydrogen bonds. Given the extended nature of the PPII conformation, one might expect the side chains to possess significant conformational entropy compared to more compact conformations. The side chain conformational entropy, Y.S ppn (T = 298°K), available to each of the residues simulated in the Ac-Ala-Xaa-Ala-NMe peptides above was estimated using methods outlined in Creamer (2000). In essence, conformational entropy Scan be derived from the distribution of side chain conformations using Boltzmann s equation... 

TMDs usually consist of a helix. The peptide bond is intrinsically polar and can form internal hydrogen bonds... 

The average conformation of an a-helix-forming polypeptide was formulated first by Zimm and Bragg (4) and then by several authors (5-9). A comprehensive survey of these theories can be found in a book by Poland and Scheraga 10) or in our companion review article (//). In this section, we outline the formulation of Nagai (5). For convenience of presentation, a peptide residue (-CO-HC R-NH-) is called helix unit when distorted to the a-helical conformation, while it is called random-coil unit when allowed to rotate about the bonds C C and C -N. These units are designated h and c. Thus a particular conformation of an a-helix-forming polypeptide chain is represented by a sequence of h and c. 

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